Background Estrogens produce several beneficial effects upon the cardiovascular system. Amongst these, an endothelium-independent effect has been convincingly demonstrated only in vitro, while there is no evidence for such an effect in vivo. The aim of the present study was to evaluate the effect of acute administration of estradiol 17β upon coronary artery reactivity to methylergometrine in 16 menopausal patients with coronary artery disease. Methods Sixteen menopausal patients underwent coronary angiography at rest and after incremental doses of methylergometrine (intracoronary 2, 10, 30 μg) before and 20 min after either intracoronary estradiol 17β (20 ng/mL at 1 mL/min for 20 min; 8 patients) or placebo (Dextrose 5%, 1 mL/min; 8 patients). Results and conclusions No significant differences were observed in baseline coronary artery diameter or area between the 2 groups. No significant differences in the degree of coronary artery constriction were observed after either estradiol 17β or placebo at submaximal doses of methylergometrine. However, the degree of coronary artery constriction after maximal doses of methylergometrine was significantly attenuated by estradiol 17β compared to placebo (change in diameter: − 0.9 ± 4.5% vs. − 19 ± 6%, p < 0.001; change in area: − 3.2 ± 9% vs. − 32.2 ± 10%, p < 0.001). Estradiol 17β reduces coronary artery constriction following methylergometrine administration in menopausal patients with coronary artery disease. This effect may be related to the calcium-antagonist properties of the ovarian hormone. Condensed Abstract The effect of acute administration of estradiol 17β upon coronary artery reactivity to methylergometrine was evaluated by coronary angiography in 16menopausal women with CAD. The investigation was performed at rest and after incremental dose of methylergometrine before and 20 min after either intracoronary estradiol 17β or placebo. Significant differences were not observed either in the baseline coronary artery diameter or the area between the 2groups, or in the degree of coronary artery constriction after either estradiol 17β or placebo at submaximal doses of methylergometrine. Coronary artery constriction after maximal doses of methylergometrine resulted attenuated by estradiol 17β for its calcium-antagonist properties.